OVERVIEW
· Instead of being opposing forces, it’s high time nutrients and drugs teamed up to maximize the benefits for patients.
· We show you how, by taking this joined-up approach, you can get the most from your medication, and at the same time, minimize adverse side effects.
· From aspirin and statins to proton pump inhibitors, we focus on the most commonly prescribed drugs and give you the lowdown on how to safely combine them with nutrients for maximum benefit.
· We also sound a note of caution when it comes to choosing your nutritional supplements – not all are created equal.
A century ago, Thomas Edison envisioned the future of medicine. In this brave new world, doctors would have no need to prescribe drugs. Instead, educating their patients about diet and lifestyle would be all that was needed to prevent disease.
Naturally, we dig Edison’s vibe. It would be easy enough to take up his mantle and make this our mantra. But deep down we know that’s neither realistic nor desirable. As we’ve seen, the way in which medicine increasingly creeps into every nook and cranny of our lives is disturbing. As too is the fact that many of our diseases could be more effectively prevented and treated by changing diet and lifestyle, not pharmaceuticals. We’re backing all that to the max. Yet we prefer to live in the real world and fully accept that drugs have an important place. When used appropriately, they have an indispensable role to play in our battle against disease.
Joined-up healthcare
It’s when changes to diet and lifestyle just aren’t going to cut it that a drug-based approach becomes more appropriate, and sometimes pills are the best solution. Actually, we think there’s an unhelpful segregation between nutrition and drugs, accompanied by the erroneous idea that you either opt for one or the other. We see it all the time. At one extreme there are people who go all out down the ‘natural’ route and shun drugs (sometimes with grave consequences); at the other, there are those people with prescription in hand who think there’s no longer any point in following a healthy diet and lifestyle.
But the two aren’t mutually exclusive. Isn’t the purpose of the medical profession supposed to be the improvement of health and wellbeing? Yet how often do we hear that doctors are unwilling to embrace a holistic approach with their patients, burying their heads firmly in the sand when it comes to any talk of nutrition? Sadly, this stance is based on pure ignorance. One of the big problems with some drugs is that they deplete the body of nutrients, causing unpleasant side effects. In this scenario, all that needs to happen is that the depleted nutrients be replaced. Hardly rocket science, but how often does it happen in practice? A more ‘joined-up’ approach makes a whole lot more sense. Nutrition should sit there, side by side, with drug treatments. This would improve the outcome for you, the patient, would often mean that a lower dose of a drug could be used, and to top it off, help reduce unwanted side effects.
In fact, it is high time things changed, so we’re going to give you the lowdown on some of the most commonly prescribed drugs. So if you want to know how to get the most benefit out of your medication, with the least adverse effects, read on.
Let’s face it, with over 120 million prescriptions for aspirin, statins and proton-pump inhibitors dispensed in England alone each year1, and hundreds of millions in the USA2, understanding how to optimize these medicines makes sense.
Aspirin
Aspirin is a household name. It has anti-platelet effects, which basically means it prevents blood clots from forming. In patients at risk, it helps to protect against stroke and heart attack. Only low doses need to be taken to achieve this effect (.75mg), which means it’s generally deemed pretty safe. However, there are still problems attributable to its use, which you’d be well advised to know about and take some simple steps to prevent.
Top of the list of problems is that aspirin can cause ulcers and bleeding, especially in the stomach. This happens even with the ‘baby’ doses used for cardio-protection. Low-dose aspirin therapy is implicated in 9% of cases of bleeding ulcers in people over 603. What’s worrying is the fact that when it comes to stomach bleeds and ulcers, you could have them but wouldn’t even notice until they get progressively worse. With millions of folk popping aspirin on a daily basis, stomach bleeds are a worrying side effect. If there was a really simple, safe and affordable way to reduce that risk, you’d want to know about it, right?
Well, we know just the thing. The lining of the stomach is the body’s largest store of vitamin C. Incredibly, it holds 25 times the levels found in the plasma4. As we said earlier, both too many and too few antioxidants are bad for you. Not only can aspirin deplete levels of vitamin C in the body, it also causes oxidative stress by increasing the free radical nitric oxide in the stomach. Simply adding in some vitamin C can restore nitric oxide back to normal levels and activates protective gut proteins5,6, which combines to reduce the risk of damaging your stomach lining7,8. A modest supplemental dose of 100–200mg per day should confer benefits.
The other problem is that for some people, aspirin simply doesn’t work. In 5–6% of people who need the drug (some scientists believe it is as high as 26%) there is no therapeutic benefit9,10. This is known as ‘aspirin resistance’ and susceptible patients experience a near fourfold increase in cardiovascular events11,12. Doctors will typically overcome this glitch by increasing the dose. But this is not always successful and means that the risk of toxicity is increased too. Upping the dose to 150mg increases the bleeding risk by over 40% and when you go higher still (300mg per day) it rises to 70%3. However, keeping the aspirin dose low (75mg) and adding a daily dose of fish oils (a combined dose of EPA/DHA of 2.4g per day) has been shown to achieve the same effect as increasing the aspirin dose to 325mg per day9.
It has been suggested that fish oils thin the blood and taking them alongside aspirin increases the risk of bleeding. A comprehensive review of the studies concluded that no risk at all existed using doses of omega-3 in the range of 1–4g per day13.
The incidence of cardiovascular disease is higher in diabetics, making them particularly strong candidates for aspirin therapy. Unfortunately, if you’re diabetic, you’re also more likely to be aspirin resistant. If that double whammy isn’t bad enough, you’re also far more likely to suffer bleeding events (by as much as 55%)14. That makes higher doses of aspirin pretty much a no-no. In fact, even low-dose aspirin should be used with caution by diabetics. It appears to be a no-win situation. Adding fish oils to the low-dose aspirin could enable diabetics to reap the benefit and reduce the high risk of side effects.
Concerns have been raised that fish oils reduce glucose tolerance, specifically in diabetics. A meta-analysis of 26 trials of type II diabetic patients showed no negative impact on glucose measures at up to 3g EPA/DHA per day15.
Statins
In medicine, statins are seen as wonder drugs, no less than a modern-day panacea in cardiovascular health. Held in the highest esteem, they are the most widely prescribed cholesterol-lowering drugs. And they’re effective. They drastically lower LDL cholesterol, reducing coronary events and decreasing mortality rates. Unfortunately, their use is hampered by their sizable side-effect profile. Clinical trials have found that less than 5% of people report muscle-related adverse effects, cognitive and memory problems or elevated liver enzymes16, yet when this is translated into clinical practice, where the user characteristics are not so neatly defined and controlled, it appears that as many as 20% experience adverse effects16. When you consider that one in four adults over 45 now take a statin (a tenfold increase over 14 years)17, these side effects quickly become a substantial public health problem. Needless to say, as the dose increases, so does the toxicity, which makes it desirable to prescribe the lowest possible dose to patients.
With the side effects of statins firmly in our mind, we can’t help but be confused that recommendations for plant stanols (part of the phytosterol group) are not more prevalent. These occur naturally in plants and are produced commercially and added to foods. You’ve probably seen cholesterol-lowering spread or yogurts advertised on TV, and that’s all we’re talking about, nothing fancier. It just so happens that plant stanols are the perfect complement to statin therapy, but how often do you hear doctors recommending them to their patients? If it would mean taking a lower dose of statins, you’d think they’d jump at the chance.
The evidence for phytosterols is so strong that the EU has authorized health claims to be made for them as a functional food, an approval it doesn’t give out too easily.
Whereas statins work on the liver to reduce cholesterol production, the plant stanols prevent cholesterol being absorbed in the gut. Combining a plant stanol with a statin creates the perfect one–two knockout strategy for high cholesterol levels. For a patient already on statins, taking a product that contains 2–2.5g of plant stanols daily reduces LDL cholesterol by a further 10% or more18,19. Compare these results with the effects of doubling the dose of a statin drug, which would typically only bring about a further 6–7% drop in LDL cholesterol20,21. It gets better. Unlike the statins, plant stanols are virtually free of any side effects. Even if you’re not on statins but have high cholesterol (say, over 5mmol/L or 200mg/dl), incorporating plant stanol-containing products into your diet will bring benefits22,23.
Plant stanols have been shown to have small effects on lowering body levels of the beneficial carotenoids (primarily beta carotene)24,25. This can easily be overcome by consuming a diet rich in fruit and vegetables, of which at least one serving has a high carotenoid content (e.g. carrots, sweet potatoes, pumpkins, tomatoes, apricots, kale, spinach or broccoli).
Some companies use plant sterols instead of stanols in their products. The cholesterol-lowering effects are initially the same, but there is a suggestion that sterols may contribute to the furring-up of arteries and actually promote coronary heart disease26,27,28, as well as becoming less effective at lowering cholesterol over time18,29. We therefore recommend that you only purchase products containing ‘stanols’.
Make sure that you don’t take more than 2–2.5g of plant stanols a day. Increased intake exerts no extra benefit but will cost you more money. It has been shown to be extremely difficult to ingest this amount on a daily basis through spreads30, requiring multiple servings per day, and thus we recommend consumption through yoghurt drinks containing the recommended 2g per serving.
The problem with statins, and indeed much of what we hear about coronary heart disease today, focuses on LDL cholesterol as the only baddie. The fact is that all cholesterol, with the exception of HDL, is harmful when high. Ideally, what we should really be talking about is ‘non-HDL cholesterol’ – that’s your total cholesterol minus your ‘good’ HDL cholesterol. This includes LDL cholesterol, and also VLDL cholesterol.
The thing about VLDL cholesterol is that it carries triglycerides, an established cardiovascular risk factor. So, what you find is that, for every 1% reduction in non-HDL cholesterol from taking cholesterol-lowering drugs, there’s a 1% decrease in the risk of coronary heart disease31. But the problem with statins is that while they can reduce VLDL/triglyceride levels, their effects are not overly strong and often require high doses, which as we know is undesirable. The upshot is that while you may have achieved ideal LDL levels on your statin therapy, your risk of heart disease can still be high32. Data from the USA shows that about one third of the population has triglyceride levels above 150mg/dl and 16% above 200mg/dl, which is classified as high risk33.
The American Heart Association classes fasting triglyceride levels of <100mg/dl as optimal, <150mg/dl as normal and 150–200mg/dl as borderline high.
Yet again, when the pharmaceuticals fall short, we find effective remedies in food. Fish oils are already recommended by the American Heart Association (AHA) for people with coronary heart disease, with just under 1g per day of EPA/DHA reducing non-fatal heart attacks, nonfatal strokes and death by 15%34. The Japanese diet typically provides such an amount35, and they have extremely low levels of coronary death. Just compare this with the average Western diet, which contains a measly 100–200mg of EPA/DHA per day36 and where heart disease is rampant. Yet at even higher doses, fish oils are effective triglyceride-lowering agents. The AHA recommends 2–4g of EPA/DHA to be taken daily (under a doctor’s supervision) to lower elevated triglycerides33. At the upper end of the dose range, reductions in triglycerides by as much as 30% can be expected33. Even the lower heart-protective doses of fish oils will still confer some, albeit attenuated, triglyceride-lowering effect37. Used alongside statins, the reduction in VLDL results in a much greater cardio-protective effect, negating the need for ever-increasing doses of statins.
Fish oils are safe and effective and they have now been approved as prescription drugs (for example Omacor®/Lovaza®). Why it is such a rarity for doctors to prescribe them remains a mystery. In the UK, less than half a million prescriptions are dispensed annually, compared with 50 million prescriptions for statins. So if you’ve got high cholesterol levels, make sure your triglycerides get measured too. If they’re high, speak to your doctor about prescribing fish oils.
Something fishy going on
Asking your doctor to prescribe fish oils – what’s that all about? Why not just cut out the middle man and buy them over the counter yourself? It might sound a whole lot simpler but it isn’t always the smart choice. First, your doctor needs to know about the supplements you take in order to properly prescribe your medications. But there’s more to it than that. All the best scientific trials – showing a triglyceride-lowering effect from fish oils – have been conducted with pharmaceutical-grade products. They use fish oil in the ethyl ester form, which provides a much higher EPA/DHA concentration (84%) compared to standard over-the-counter preparations (usually only 30%). Although all concentrations lower triglycerides, it’s thought that we need the higher-concentration products for the best effects.
Then we get down to purity. Dietary supplements don’t undergo the same rigorous quality analysis as prescription medicines, which go through a process of meticulous testing, and abide by strict limits for potential contaminants. Environmental nasties like heavy metals, PCBs and dioxins (all carcinogenic above certain levels) are among the potential toxins prevalent in fish oil. Needless to say, you want to avoid them if you possibly can.
While we revel in getting stuck into the ‘evil’ drug industry, we take great comfort in thinking that the manufacturers of our nutritional supplements are part of an altruistic cottage industry that holds our health in the highest regard. Sorry to disappoint. Studies of common brands of fish oil supplements have found huge noncompliance with recommended dioxin levels. And we really should point out that these were for mainstream sale in the UK and Ireland, not some dubious backstreet products:12 out of 33, and ten out of 15 supplements tested were found to have levels above those deemed tolerable daily intakes38.
In 2002 and 2006, the EU introduced new limits of exposure to these noxious contaminants. But even against the might of the EU, it seems the unscrupulous were undeterred. In 2010, a European Food Safety Authority report of more than 7,000 food and animal feed products found 8% of samples had dioxins and dioxin-like PCBs exceeding maximum EU levels, with fish-related products coming out worst of all39. On top of this, fish oils are very unstable. If they aren’t manufactured correctly and safely, unpleasant degradation products, such as peroxides and aldehydes, can form. These not only negate the benefits of fish oils supplements, but have the potential to cause harm40. We’re pretty sure that the last thing you’d want to be doing is taking something to prevent heart disease, only to be unwittingly increasing your chances of cancer.
Just as there are some suspect products out there, there are some top-notch, high-quality ones too, so if you are going to use over-the-counter fish oil products, don’t just pick the cheapest or the first one you see. Look for the one with the highest concentration of EPA and DHA, and always check for assurances of quality – ideally the GMP (Good Manufacturing Practices) certification. This way you can be assured of the closest match to pharmaceutical standards. And remember, for a significant triglyceride-lowering effect, you need one that provides 2g plus of EPA/DHA per daily serving.
COQ10
If you take statins, you may have seen advice to take a nutritional supplement called Coenzyme Q10 (CoQ10 for short). It’s one of the few examples of healthcare professionals recommending a nutrient to complement drug therapy. CoQ10 is vital for energy (ATP) production, as well as having antioxidant properties. Statins significantly deplete serum CoQ10 levels and this has been suggested as a reason for the muscle and liver problems, fatigue and possibly even the lack of benefit in heart failure. In fact, in 1989 the pharmaceutical giant Merck filed two US patents for combining CoQ10 with statins to prevent the associated muscle and liver damage. But these patents were never acted upon.
However, studies have not shown clear benefits of giving CoQ10 alongside statins. First, and contrary to what you’ll hear most people saying, statins don’t actually deplete serum CoQ10 levels. CoQ10 gets carried around in LDL particles. Since statins reduce LDL levels, this will have the effect of reducing the total amount of CoQ10, too. The amount of CoQ10 per LDL particle – which is what’s important – actually remains the same or even increases41,42,43,44. There’s another glitch. Serum measurements of CoQ10 are pretty much useless. That’s because levels in the serum don’t correlate with intracellular levels and the effects on tissues such as the muscles or liver41,42,45, the very places where statins might cause a problem. So you can begin to see why measuring serum levels and then jumping to a whole lot of conclusions is a waste of time.
Studies that have taken biopsies of muscles have shown that some depletion in cellular energy production can occur from high-dose statins, but overall studies have been rather hit and miss41,46,47. This brings us nicely on to the second problem, and a flaw that permeates the scientific research, and that’s a case of bad planning. All these trials have been conducted with small populations, often less than 50, and sometimes as few as 20 subjects. But the occurrence rate for muscle problems in clinical trials is less than 5%. In science there is a useful ‘rule of three’, that to be 95% sure that CoQ10 depletion does not occur in the 1–5% of individuals with muscle problems we would need to test a minimum population of 60–300 plus individuals. Performing studies with fewer people simply adds up to a big fat waste of time. The truth is that we may as well take the money, go to Vegas and hit the roulette tables – red it depletes levels, black it doesn’t.
Even if statins do deplete tissue levels of CoQ10, being observational findings these are just associations and still don’t prove that this is what is actually causing the problems. For proof, we need to see whether adding CoQ10 cures the problem. While such ‘intervention’ studies have been small and poorly conducted, their findings do suggest a positive effect of CoQ10 supplementation at 100mg per day in patients with muscle-related symptoms48,49.
The whole field of statins and CoQ10 has woven itself into a labyrinth of confusion. However, as we disentangle fact from fiction, it does appear that, in susceptible individuals, tissue levels of CoQ10 can become depleted. While still unproven, there is a notable absence of side effects from taking CoQ10, and supplementation of 100mg per day is a prudent measure, especially for those on high-dose statins. Until more conclusive studies are published, however, a more favourable approach is to incorporate plant stanols and fish oils into your regime, which will help you to use the lowest possible dose of statins.
In Japan and certain European countries, CoQ10 has now been granted a prescriptive licence in the treatment of heart failure and ischaemic heart disease50.
Proton Pump Inhibitors
Proton Pump Inhibitors (PPIs) shut down acid production in the stomach, making them a mainstay prescription for the treatment of ulcers and acid reflux disorders. They bring noticeable symptomatic relief and, being perceived as safe drugs, doctors have no problem in prescribing them. In fact, a rampant culture of over-prescribing exists. A staggering 113 million plus prescriptions in the USA51 and 36 million plus prescriptions in England1 are dispensed annually. Study authors have suggested that they are being inappropriately prescribed for 25–70% of patients52. What makes those stats even more disturbing is the fact that we now know these drugs charge a heavy premium on our health.
Most worryingly, their long-term use depletes calcium from the bones. The occurrence of hip and spine fracture goes up by about 45– 60%, an effect observable within just one year of use53. In one study, taking PPIs for seven or more years was associated with almost doubling of risk of an osteoporosis-related fracture. The risk for hip fracture was almost five times greater!54 The risk has been described as being ‘similar in size to those for other established osteoporotic-fracture risk factors, such as smoking, low body mass index and excessive alcohol intake54.
The biggest problem is that it appears one can’t alleviate the problem simply by taking extra calcium. A large study observed that the condition appeared in PPI users independent of calcium intake55. How the increased risk is conferred is not actually known, but it could be due to an interaction of the parathyroid gland and vitamin D levels. It’s possible that by keeping vitamin D levels optimal, the risk will be reduced, but for now this remains unproven.
On top of this, in a small proportion of patients PPI use can deplete levels of magnesium, a mineral that is also essential for bone health56,57,58,59,60. Magnesium depletion is becoming increasingly prevalent, to the extent that the FDA now recommends testing levels before and during prolonged PPI treatment. We can only conclude that it would make a lot of sense for anyone on long-term PPI treatment to ensure a plentiful dietary supply of magnesium from foods such as green leafy vegetables, nuts, wholegrain cereals and fish.
A further problem with acid suppressant tablets is the risk of vitamin B12 deficiency. We need stomach acid to liberate B12 from our food so that we can absorb it. Studies have shown that deficiency can occur in elderly people taking PPIs61,62,63 and even taking a standard dose supplement providing the daily requirement of B12 is insufficient to restore levels63. When it comes to PPIs, the greater the dose and the greater the duration of treatment, the greater the risk of B12 deficiency becomes.
The thing with vitamin B12 is that we don’t actually need a full-blown clinical deficiency to experience adverse effects. Even moderate depletion can raise levels of homocysteine in the blood. In one study, clinical B12 deficiency occurred in about one in 10 PPI users, yet raised homocysteine levels were found in approximately one third64. High homocysteine levels are associated with an increased risk of a plethora of afflictions, including dementia, reduced bone density and cardiovascular disease. Long-term PPI users should have their B12 and homocysteine levels monitored. If low B12 levels are evident, oral supplementation of a dose greater than the RDA (about 4–5mcg) should be taken.
It’s not just nutrient depletion that you need to be concerned about with PPI use either. Stomach acid is a pivotal defence mechanism against infection. Without acid, ‘bad’ pathogenic bacteria can colonize our intestine, causing infection. Clostridium Difficile is a serious infection, and its incidence is growing rapidly. It can extend hospital stays by as much as 36 days65and for some it can be deadly. In PPI users its occurrence is increased 74%66. Probiotics – such as lactobacillus acidophilus, lactobacillus casei and Sacharomyces boulardii – will colonize the gut, protecting gut integrity, as well as having antimicrobial properties that can help to reduce infection risk67,68,69. However, the effects of probiotics are short-lived – usually just one to two days – so you would need to take them for the whole period that you are using the acid-suppression therapy. Probiotics may not be suitable for some patient groups (e.g. immuno-compromised), making it important to discuss this recommendation with your physician.
THE PARTING SHOT
While drugs have an important role to play, an attitude of ‘in drugs we stand alone’ surely has no credible place in healthcare fit for the twenty-first century. Often they cause significant nutrient depletion, or interfere with the body’s important physiological functions. More often than not, careful use of nutrients in conjunction with conventional treatments would lessen the need for high-dose drug treatments and banish many of the side effects.
It’s pretty clear that, when it comes to ‘total’ patient care, it’s high time that most doctors went back to school.
SUMMARY AND RECOMMENDATIONS
· If you take aspirin to reduce the risk of stroke and heart attack, a simple low-dose vitamin C supplement of 100–200mg per day may reduce the risk of stomach ulcers and bleeding.
· If you are among the minority of people who don’t respond to low-dose aspirin, you can enhance the treatment by taking a high-dose fish oil supplement, rather than increasing the dose of aspirin, which runs the risk of unwanted side effects.
· If you have high cholesterol levels, you should consider the use of plant stanols, which are widely available in cholesterol-lowering yoghurts. These can enhance the effects of statins, which means a lower dose of medication can be used.
· If you have elevated triglycerides, a risk factor for heart disease, ask your doctor to prescribe fish oils to lower them. Prescription fish oils are preferable to over-the-counter versions, some of which are of questionable potency and purity.
· If you take high-dose statins, you may consider supplementing 100mg per day of CoQ10, although we recommend using plant stanols and fish oils first to see if they can reduce the need for high-dose statins in the first place.
· If you take PPIs, it is advisable to ensure a plentiful dietary intake of nutrients needed for bone health, including calcium and magnesium, while optimizing your vitamin D status (see Chapter 7).
· Vitamin B12 and homocysteine levels should be monitored if you take PPIs long-term – you may need a vitamin B12 supplement of 4–5mcg per day.
· If you take PPIs, you may also consider supplementing with a good quality probiotic to keep ‘bad’ bacteria at bay.
· But remember: all changes affecting your medicines must first be discussed with your physician or health professional.