Sports supplements to die for?

The worst thing that can happen when experimenting with new sports supplements is to discover that they don’t work – right? Wrong. Andrew Hamilton explains why some supplements could leave you with more than a hole in your wallet…

By the time you read this, the Christmas festivities will be well underway and most of you will be enjoying a bit of down time from your normal training regime. With less training miles under the belt and more food and drink past the lips, many athletes will resume training with a few pounds to shed. And while an increase in training volume will help shed the excess, some might be tempted to look for nutritional means of support such as fat-burning nutrients to help speed up the process. This option can be appealing at other times of the year too – for example in the run up to an event where a runner or cyclist is looking to maximise his or her power-to-weight ratio. But is this really an effective option? And perhaps a rather more alarming question is whether this is a safe option?

Is natural safe? Supplements to enhance performance and (especially) weight loss are hugely popular across the globe. According to the latest research study released by Technavio, the global weight-loss supplement market is expected to reach around 4.8billion USD by 2020^{www.technavio.com/report/global-health-and-wellness-weight-loss-supplement-market?utm_source=T4&utm_medium=BW&utm_campaign=Media}. Although the dividing lines aren’t clear cut, we can categorise weight-loss supplements into three broad categories shown in box 1. It’s natural to assume that of these, only pharmaceutical products and medicines carry a significant risk of harmful side effects. But while many products in this category undoubtedly do (that’s why they’re sold and prescribed through pharmacies and doctors), some nutrients can also carry risks. For example, it’s long been known that very high doses of vitamin A can produce toxicity.

However, what is less appreciated is that although natural, many extracts of herbs and plants can produce significant side effects, some of which are serious. These risks are multiplied when combinations of herb or plant supplements are taken. Indeed, in recent years, a number of cases of hospitalisation resulting from the use of herbal weight loss supplements have occurred – some of which have resulted in fatalities. In a nutshell, just because a supplement only contains a concentrated plant extract (and is therefore considered or even labelled as ‘natural’), that doesn’t mean it is safe. In this article therefore, we will explore the safety or otherwise of some of the more popular products, and make recommendations for safe routes to weight loss.

Although the exact prevalence of plant/ herb supplement consumption is unknown, we do know that these supplements are widely used across the globe. For example, it’s estimated that more than 50% of the US adult population uses herbal supplements^{J. Nutr. 2011, 141, 261–266}. On this side of the Atlantic, a recent survey looked at herbal supplement use in Finland, Germany, Romania, Italy, Spain, and the United Kingdom. It found that 18.8% out of 2359 consumers were using herbal supplements^{PLoS ONE 2014, 9, e92265}. You might assume that with so many people using herbal supplements, they must be pretty safe. The reasoning goes like this: not only are they ‘natural’ products, because they’re so widely used, you’d soon know if they weren’t safe. However, herbal supplement use is not as safe as many people believe. These products can induce adverse effects, the most common of which is liver injury. Indeed, it turns out between 2% and 18% (nearly one fifth) of all identified cases of drug-related liver damage (hepatotoxicity) are caused by herbal supplement use, and the rate of herbal supplementinduced hepatoxicity is growing rapidly^{Gastroenterology 2005, 129, 512–521 Rev. Esp. Enferm. Dig. 2008, 100, 688–695 Hepatology 2014, 60, 1399–1408}. In Asia, where herbal supplements are much more widely used, herbal supplements account for 73%, 71%, and 40% of drugrelated liver damage in Korea, Singapore and China respectively^{Am. J. Gastroenterol. 2012, 107, 1380–1387 Liver Int. 2007, 27, 465–474 Eur. J. Gastroenterol. Hepatol. 2013, 25, 825–829}!

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BOX 1: WEIGHT LOSS SUPPLEMENT CATEGORIES

Nutrients – these are vitamins and minerals present naturally in the foods we eat and which are essential for health. The theory is that a shortfall in a particular nutrient – for example iron – could interfere with normal energy metabolism, resulting in tiredness/fatigue and reduced energy expenditure, which makes weight gain more likely. Boosting these missing nutrients helps to correct any imbalance or shortfall.



Herb/plant extracts – these contain natural occurring and biologically active compounds present in foods and herbs, which are often purified and concentrated to deliver high levels of an active ingredient. This means that the consumer doesn’t have to consume large quantities of a food or drink in order to get the amounts of the active ingredient required to produce an effect. Examples include: green tea extract, garcinia cambogia extract, raspberry ketones etc.



Pharmaceutical products – These are products (often synthetic) that are usually prescribed by a doctor, or which are only sold through pharmacies. Depending on the product, a prescription from a GP may or may not be required. This category also includes drugs that are used to treat certain medical conditions, but which may have a weight-loss/performance-enhancing effect when taken by athletes – for example anabolic steroids and stimulants. Such products are of course generally banned in sport and many are well known to have harmful side effects.

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THE HERBAL SUPPLEMENT LOTTERY

The risks from medicinal drugs are well understood, but how is it that herbal supplements, which most would deem to be safe, are riskier than is generally realised?

To become approved as a medicine, pharmaceutical drugs have to undergo extensive testing. This means that safe maximum dosage levels are determined along with long-term safety. Also, most medicinal drugs will produce side effects, but these are generally well documented in the literature that arises out of testing. Such detailed testing is possible because most drugs are based on a precisely known amount of a single active chemical compound, whose underlying mechanisms of action in the body are already well understood. This also allows researchers to look at possible problems where the use of the drug is contraindicated. This includes drug-drug interactions, or where patients are suffering another medical condition that could be adversely affected.

Now compare this with herbal supplements. First of all, even single herb extracts may contain dozens or even hundreds of active chemical compounds in addition to those that exert the desired effect. Secondly, the method of extraction and preparation can mean wildly varying levels of active ingredients. For example, one 500mg green tea extract capsule could contain just a few milligrams of the key active ingredient (epigallocatechin gallate) or over 200 milligrams. This will depend on the exact green tea variety as well as processing (see figure 1). Unless you take your product to the lab, it’s hard to know exactly what you’re getting. Thirdly, a number of herbal supplement products contain combinations of ingredients, which may include vitamins, minerals, amino acids, herbs and botanicals (or extracts of) – which dramatically increases the chances of unwanted interactions.

FIGURE 1: EPIGALLOCATECHIN GALLATE CONTENT OF DIFFERENT VARIETIES OF (UNPROCESSED) GREEN TEA

In addition, herbal supplements (because they’re concentrated extracts of edible plants) don’t go through the same rigorous process of analysis before being brought to market as do drugs. This often means little is known about maximum safe doses, herb-herb and drug-herb interactions, or when a herb could be contraindicated in a certain medical condition. In short, while many herbal supplements are safe for most people in most circumstances, there are a lot of unknowns, which can result in health risks for unsuspecting consumers.

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The bad and the ugly

There are dozens and dozens of different herbal weight loss supplements on the market so it’s beyond the scope of this article to examine the evidence for and against the safety of each and every one. However, for some of these, enough evidence has accumulated in recent years to raise some serious concerns, and in this section, we’ll look at a few of these.

GREEN TEA (CAMELLIA SINENSIS) EXTRACTS

Green tea is a popular drink consumed across the globe, and one that has been used for centuries. Green tea contains methylxanthine alkaloids (such as caffeine and theobromine), and antioxidant polyphenols, which are considered the major bioactive molecules of tea. While drinking green tea infusion is generally safe, green tea extracts have shown to have a liverdamaging (hepatotoxic) potential.

The first report on liver damage related to green tea extract intake was in 1999. Since then, many cases of liver injury related to the intake of different green tea extracts have been recorded^{Liver Int. 2011, 31, 595–605 Arch. Toxicol. 2015, 89, 851–865}. In a review of 216 case reports (which occurred in the US, UK and Australia) by the US pharmacopeia cases, 27 were labelled as ‘probably induced’ by green tea extracts, with the remaining seven labelled as ‘possibly induced’^{Drug Saf. 2008, 31, 469–484}. In one of these cases, the patient died, which indicates that this kind of hepatotoxicity can have serious outcomes.

Exactly how green tea extract may cause liver damage in unclear, especially as we know that drinking green tea can actually protect against liver cancer^{Liver Int. 2008, 28, 990–996}. The most likely explanation is that some extracts contain very high levels of epigallocatechin gallate, which in the longer term can induce oxidative stress leading to damage. Severe liver damage that required liver transplantation has been associated with a supplement called ‘Exolise’. This was an alcohol extract containing a huge 25% by weight of epigallocatechin gallate and 5%–10% caffeine^{Eur. J. Gastroenterol. Hepatol. 2005, 17, 1135–1137}. Thankfully, Exolise was withdrawn from the market (in Spain) in 2003 by the Spanish Drug and Sanitary Products Agency, AEMPS.

While there are some cases of liver injury due to green tea extracts alone, in many cases the patients also are taking other drugs or products with potential hepatotoxicity. In one case, a 28-year-old female bodybuilder consumed a herbal product called ‘Somalyz’ (which contained a combination of usnic acid, propionyl-Lcarnitine, phosphatidylcholine/ phosphatidylethanolamine, gamma-aminobutyric acid, and vitamin E) and ‘Lipolyz’ (containing green tea extract, usnic acid, propionyl-L-carnitine, cyclic adenosine monophosphate and vitamin E)^{Can. J. Gastroenterol. 2011, 25, 157–160}. After developing severe brain swelling, she survived but required a liver transplant.

USNIC ACID

Usnic acid is uniquely found in lichens, and is especially abundant in lichens such as Alectoria, Cladonia, Usnea, Lecanora, Ramalina and Evernia. Many lichens and extracts containing usnic acid have been used in perfumes, medicines and cosmetics thanks to the antimicrobial, anti-inflammatory, antioxidant, analgesic, and weight loss properties. When used in weight-loss products, usnic acid is often combined with other herbal products.

In the body, usnic acid functions as an ‘uncoupler of the mitochondrial respiratory chain’. In plain English, it stimulates fuel oxidation and increases calorie burning rates, which could aid weight loss^{Chem. Biol. Interact. 2013, 203, 502–511}. Unfortunately however, this mechanism is known to generate oxidative stress, which can damage energy-producing cells along with those in the liver.

Several cases of acute liver failure related to usnic acid alone or in combination with other herbal supplement products have been reported, including cases requiring liver transplantation^{Ann. Intern. Med. 2002, 136, 590–595 Am. J. Gastroenterol. 2004, 99, 950–952 Mayo Clin. Proc. 2006, 81, 541–544 Arch. Surg. 2003, 138, 852–858 J. Hepatol. 2004, 41, 1062–1064}. An example of this is hepatotoxicity has been described relating to the intake of a multi-ingredient product called ‘LipoKinetix’, which contains usnic acid along with norephedrine, caffeine, yohimbine, and diiodothyronine.

In one study, researchers described seven cases of acute liver injury related to LipoKinetix^{Ann. Intern. Med. 2002, 136, 590–595}. The typical time to onset for liver injury usually occurred within the first three months of consumption and in one of these cases, the patient developed acute liver failure. Other causes of liver injury were excluded in all the patients. Thankfully, all recovered spontaneously after discontinuing use of LipoKinetix, and results of liver tests (as well a symptoms) normalised within four months.

In another study, a case series of acute liver failure from an adult tertiary care university hospital and a Veterans Affairs centrewas analysed. This described 20 cases of liver failure; in ten cases, the patients were either recent or active users of herbal supplements. In two of these cases - a 25-year-old female who sadly died and a 42-year-old male who recovered - Lipokinetix was identified as the only cause of liver failure^{Arch. Surg. 2003, 138, 852–858}. Following these cases, the US Food and Drug Administration (FDA) published a warning about LipoKinetix, and the product was withdrawn from the US market in November 2001.

Other cases of supplements containing usnic acid include that of a 28-year-old woman who developed ALF and required orthotopic liver transplantation after two weeks of intake of pure usnic acid for weight loss^{Am. J. Gastroenterol. 2004, 99, 950–952}. In another, two cases of severe liver toxicity related to a multi-ingredient health supplement called ‘UCP-1’ (containing usnic acid, L-carnitine, and calcium pyruvate) were reported^{Mayo Clin. Proc. 2006, 81, 541–544}. They involved acute liver injury in a wife and husband after taking the product for bodybuilding purposes. The wife subsequently developed liver failure, which required liver transplantation. Although usnic acid has now been dropped from many weight loss supplements, a quick search on Google shows that it is still readily available and on sale.

3.1. MA HUANG EXTRACT

Ephedra, also known as Ma huang, is a medicinal preparation from the plant Ephedra sinica and is widely used as a weight-loss product by millions of people. A wide variety of compounds have been identified in various species of ephedra of which the most common are ephedrine and pseudoephedrine, which are the sources of its stimulant and thermogenic effects. These compounds stimulate the brain, increase heart rate, constrict blood vessels (increasing blood pressure), and expand bronchial tubes (making breathing easier). Their thermogenic properties cause an increase in metabolism, as evidenced by an increase in body heat.

Analysis of safety data from 50 clinical trials have revealed that ma huang is associated with many adverse events related to products containing it. These include psychiatric, gastrointestinal, cardiovascular and cerebrovascular (eg strokes) problems^{J. Am. Med. Assoc. 2003, 289, 1568–1570}. Liver injury associated with ma huang has also been reported.

In an analysis at four transplant centres, ten patients with severe liver injury were analysed. All had used products containing ma huang for weight loss. These products included Xenadrine, Excelerator, Metabolife 356, Thermolite, BetaLin, Thermo diet stack and Hydroxycut^{J. Hepatol. 2004, 41, 1062–1064}. The typical time to onset was approximately six weeks or more and the patients presented with hepatic encephalopathy (liver swelling). Three of these patients required liver transplantations, while the remaining seven recovered without residual lesions.

GARCINIA CAMBOGIA

Garcinia cambogia is a plant-based supplement widely promoted for weight loss. Garcinia cambogia (also known as Malabar tamarind) is a small fruit that has been traditionally used to enhance the culinary experience of a meal. It is a very good source of compounds known as hydroxycitric acids (structurally related to citric acid found in citrus fruits) and one of these (known as (-)-hydroxycitric acid), is thought to assist with weight control by helping to inhibit fat synthesis in the body.

Garcinia cambogia has been implicated in hepatotoxicity in patients taking Hydroxycut, which contains a variety of ingredients, including Garcinia cambogia. The use of Garcinia cambogia alone has also been implicated in cases of hepatotoxicity. In one case, a 52-year-old female needed a liver transplant after taking Garcinia cambogia for weight loss (USA Nutra Labs – 2 x 1000mg capsules daily) for 15 days^{Ann. Hepatol. 2015, 15, 123–126}. Another case occurred in a 42-year-old female after taking pure Garcinia cambogia for one week in order to lose weight^{J. Clin. Gastroenterol. 2015, 49, 449–450}. She was found to have very high levels of liver enzymes associated with liver damage. Fortunately, after several days, the patient recovered and was discharged. In both cases, all other causes of liver injury were ruled out.

A different approach

The herbal supplements described above represent only a few of the many dozens on the market that are purported to aid weight loss. The increasingly globalised nature of the health and fitness industry means that many more (previously little known) herbal supplements are appearing on the market, and for many of these products, data on efficacy and safety are completely lacking. To make matters even more confusing, the formulations of these products frequently change - including the amounts and varieties of the herb used, and other ingredients added.

For athletes who are seeking proven weight-loss supplements that are also completely safe, this represents something of a minefield so an obvious question is are there better, safer and proven ways than taking weight-loss supplements to lose weight and enhance endurance performance? The answer to this is most definitely yes.

While they might entail a little more thought and application, there is an array of nutritional and training tools that are proven to reduce body fat in a safe and effective manner. These include the following:

*Attend to the dietary fundamentals – No amount of weight loss supplements or training can compensate for a day-to-day diet that is fundamentally flawed. If your diet contains too much sugar, refined carbohydrates, fatty foods, processed foods, alcohol or just too many calories overall, you will struggle to maintain an optimum level of body fat. Instead, you should aim to consume a diet that includes plenty of unrefined carbohydrates, such as wholemeal bread and pasta, whole grain cereals and rice, potatoes, lentils, beans etc.

Nutrient-rich fruits and vegetables should also form a large component of your food intake – ideally you should be eating 2-4 servings of fruit per day and 3-5 servings of raw or lightly-cooked vegetables. High-quality proteins such as meat, poultry, fish, eggs, beans, nuts, milk yoghurt and cheeses should make up about 25% of your calorie intake. Processed fats and oils, sweets, processed/ junk/fast food and confectionery should be minimised and used as treats rather than as staples. If you need help planning your day-today diet, seek the help of a qualified nutritionist.

*Slow rather than quick – related to the above point is the quality of your carbohydrate intake. Sugary and refined carbohydrates should be minimised wherever possible, and slow-releasing (also known as ‘low-GI’) carbohydrates such as oats, pasta, beans, whole grain bread rice etc consumed instead. That’s because fast releasing carbohydrates are more likely to cause blood sugar spikes, which can lead to fat storage. By contrast low-GI carbs are able to fuel training without causing blood sugar spikes.

Moreover, research shows that consuming a low-GI meal before training leads to higher rates of fat burning during exercise than the same number of calories of a fast-releasing carbohydrate. For example when runners consumed two grams per kilo of bodyweight of either low-GI or high-GI carbohydrate three hours before running, fat oxidation rates were significantly higher during exercise and endurance was dramatically improved when the carbohydrate consumed was of a low GI type^{Int J Sport Nutr Exerc Metab. 2006 Oct;16(5):510-27}. The only exception to this rule is to sustain performance during prolonged exercise, or when you need to refuel rapidly after exercise. In these case, rapidly digested and absorbed (high-GI – eg carbohydrate drinks and gels) carbohydrates are preferable.

*Go easy on the drinks - while it sounds counterintuitive and goes against most conventional advice, where fat burning rather than performance is the priority, carbohydrate drinks and gels, which raise insulin and reduce fat oxidation, should be avoided. Studies show that although consuming carbohydrate drinks before endurance exercise boosts performance, the subsequent rise in blood sugar and insulin reduces the proportion of energy derived by burning fat^{J Sports Sci. 2003 Dec;21(12):1017-24 Appl Physiol Nutr Metab. 2008 Jun;33(3):441-9}. Don’t forget though you’ll still need to consume some energy-free fluid when training, especially in warm conditions.

*Try occasional fat-burning training strategies – implementing the strategies above will make a significant difference to ensuring you can shed excess weight effectively. However, there are some other dietary/ training implementations that can further enhance the fat-burning capacity of your muscles. These include time-restricted feeding (see figure 2), fasted exercise in the morning (see Chris Boardman case study) and sleep low. These are described in table 1. While the evidence that these approaches can increase fat burning is rigorous, they should be seen as occasional adjuncts to your training – not as a long-term solution. You should only try these out in training; they should not be trialled in the run up to or during a period of competition.

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FIGURE 2: TIME-RESTRICTED FEEDING

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TABLE 1 OCCASIONAL FAT BURNING STRATEGIES 2022 10 04

Diet name	Description	Evidence for benefits	Drawbacks
SLEEP LOW	A carbohydrate-fuelled high-intensity training session is performed in the evening, followed by a low-carbohydrate recovery period and overnight fast, which effectively depletes muscle glycogen for the night. The following morning, after a light, low-carbohydrate breakfast a prolonged, moderate intensity training session is performed, encouraging glycogendepleted muscles to adapt to burning fat. Carbohydrate intake is not limited but instead restricted at certain times.	*Regular sleep-low sessions appear to enhance fat burning AND improve endurance performance.	*Hunger may be experienced overnight. *Dietary approach needs planning within the context of a weekly training schedule. *Not recommended for the competitive phase
TRAIN LOW, RACE HIGH	Periodic training sessions take place in conjunction with a low-carbohydrate diet. Before racing, athletes ensure a highcarbohydrate diet and full muscle glycogen repletion.	*Fat burning is enhanced.	*No evidence for increased performance.*Low-glycogen training is tiring and increases the risk of illness and injury.
TIME RESTRICTED FEEDING	Food intake (but not calorie or carbohydrate intake) is limited to a 6-hour window each day – for example 8am to 2pm.	*A significant decrease in body fat compared to the normal diet. *Fat oxidation increased. *Adiponectin levels increased (a hormone associated with weight loss, improved glucose metabolism and better fat burning)	*Very few, but could be tricky to stick to in certain social settings. *May not suit competition.

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Case study: Chris Boardman

Retired racing cyclist Christopher Boardman is one of Britain’s most celebrated riders. Boardman took the world hour record three times in his career, as well as winning Olympic gold in the Track Pursuit and several stages of the Tour de France. One of the training techniques Boardman used back in 1990s to get and stay lean was ‘fasted rides’.

These took place on average once a week – usually at weekends - and involved a long, low-intensity morning ride. The first 60-90 minutes of these rides took place on an empty stomach – ie Boardman would set off without consuming breakfast. The goal of these rides was to increase Boardman’s fat burning capacity; riding first thing in the morning on an empty stomach (when blood sugar levels are low) is known to help enhance fat burning pathways in the muscles, which leads to a greater proportion of energy derived from the body’s stores of fat – even after exercise.

However, Chris was also keen to point out that some carbohydrate feeding must be taken after around 60-90 minutes or so and at a rate of 60 grams per hour thereafter. As Boardman himself put it: “Problem is many people who try it seem to think that you can just ride five hours with no fuel at all – little wonder that they feel terrible during and after! You must begin the feeding within an hour and a half of starting the ride.”

Boardman was guided by instinct when he undertook his pioneering fat-burning rides. In 2017 however, recent research seems to confirm that his approach fits with the science – ie these kinds of rides help to activate the body’s fat-burning genes, without the drawbacks of some of the more severe dietary approaches!

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