Anti- Ageing Supplements, Drugs and Nutrition - are they real & do they work?

How are we trying to stop ageing and is it possible?

There are a lot of theories around why we age. At the moment there are 4 main areas being explored as pathways to target to prevent ageing. There is not one way to stop ageing:

NAD - is one of the big ones being looked at. As we age NAD goes down and down. It is the energy used for a lot of DNA repair enzymes in the body.
AMP-K pathway - looking at optimising this pathway. When we stimulate M-TOR we inhibit AMP-K. These two are in balance. If we activate one we don’t want to be activating the other. When we stimulate AMP-K we stimulate autophogy.
M-TOR pathway- M-TOR- is responsible for muscle/protein synthesis. So think of it as building up the structures in the body.
Autophogy - how we stimulate this to best effects. Autophogy is the body ability to clear away old dead or not as well functioning cells. It’s believed as we age we build up these old components/organelles such as mitochondira and we do not flush them away correctly, decreasing the overall efficiency of our cells. If we can flush away these malfunctioning cells and stimulate new cell growth it is thought we can decrease the ageing process. Autophogy can be stimulated by exercise, fasting, infrared saunas, spermidine, metformin, quercetin, fisetin, and Berberine.

Why haven’t I mentioned antioxidants here?

We were very excited at one point to think that antioxidants would be the solution as they would neutralise any radical/ free radical damage in the body and keep our cells happy and functioning optimally. However the studies when direct antioxidants were administered and directly react with oxidants and neutralise them- it didn’t show the benefits we hoped. What appears to be better is stimulating our own pathways in the body that stimulate antioxidant activity. NRF-2 is the pathway and cell cascades that get rid of oxidants in our body. When we look at heart disease and specifically the cruciferous vegetables (broccoli is the most well known) that were shown to decrease mortality. Cruciferous vegetables contain glucoraphanine and microcynase and when they mix together in the gut they form sulfurofane. Sulfurone if a really potent activator of NRF2. Vit C is unique in that it is an antioxidant but it also stimulates the body natural production of antioxidants.

What are some ways to stimulate these potential anti-aging pathways ?

Spermidine

What is it?

Spermidine is a Polyamine. Our cells can make this themselves (which is why it isn’t classed as a supplement) but the levels found in our cells are highly dependant on the amount we take in through our diet and eating choices. So we can boost our levels through our diet alone and don’t need to supplement it. In mice studies it was able to suppress the age related decline in cardiovascular function and increase overall longevity by 10%. There isn’t much spermidine in meats but there is higher levels in fruits and vegetables. Vegetable sprouts, peas, mushrooms, broccoli and cauliflower have high amounts and spermidine is heat resistant- so cooking food does not decrease the spermidine levels in that item. The amount of spirmadine for example in mushrooms is 160mcg per gram where as meat has 20mcg per gram. It is readily absorbed from the gut so we get 40-80% uptake of the amount consumed.

How it works?

Stimulates autophogy pathways to clear away old cell to allow new cells to replace them. Auotphogy is “self eating”. Now with autophogy we don’t want to be stimulating this continually- ie eating ourselves away non-stop. We want to stimulate autophogy in cycles and allowing enough time in-between for our cells to rebuild themselves. It is also referred to as a calorie mimetic agent due to its autophogy effects.

In long term studies when they look at Spermidine a certain level within the diet shows that decreased death rates and cardiovascular disease as well as recused cancer risk. The SMARTAge study currently underway is looking at it’s effects on dementia and comparing it to placebo.

In the population age study with 1000 people the death rate decreased with increasing spermidine intake. In patients that are healthy at 100 years old they looked at their spermidine levels and they found those that were healthy at 100 years of age had spermidine levels comparable to people 30-50 years their junior.

Quercetin and Fisetin

Quercetin and Fisetin are both polyphenols called flavanoids. There are 1000s of polyphenols but we are just scratching the surface on what polyphenols do in the body. And we aren’t sure yet how many we should use but quercetin and fisetin have shown real promise. We do struggle to absorb polyphenols, they do like to be absorbed with a fat. So if you have it in a capsule in a supplement form with out fats you only absorb 10%. However if you have quercetin with olive oil or fish oil you get much higher rates of absorption and benefits.

Dasatinib and quercetin study in 2021 used in patients with lung scarring ie pulmonary fibrosis. They wanted to see if we stimulated autophogy would that improve long function and decrease the scarring. This was the first trial to show in human there is a benefit. Most other trials have been in mice and shown real promise. But it needs to be used in a “hit and run’ approach. Where it is taken short term and a break is given for the body to repair and rebuild.

Exercise

Now we need to just mention this anyway even though it’s not a supplement. (But maybe it should be seen as one) .

If we look at exercise purely for a longertivity perspective. It has a bell-shape curve in terms of benefits. A little bit improves your health then we hit a peak or optimum point but when we do too much it has actually been shown to increase our death rate. The “optimum” point is 4-5 days of exercise. Which again lends to this principle we was to stimulate the body but then have sufficient rest time for our body to build itself back up again. Exercise activates M-TOR. When we exercise it increases oxidative stress/damage, which we need a little bit of oxidative stress for our mitochondria (the powerhouse in our cells) to work more efficiently. Our mitochondria need to be more efficient to deal with this stress, but we don’t want to do too much. We want a combination of resistance training and cardiovascular training. Again too much of either is not great our body like balance not extremes.

Exercise triggers what’s known as hormesis, or a biological process where a beneficial effect is triggered by a limited exposure to something harmful or challenging to the body. You probably know that lifting weights causes microtears in the muscle that the body then knits back together to make it bigger and stronger. A similar process happens within cells, too: exercise causes a transient increase in mitochondrial free radicals (mitochondria are the energy factories within your cells). Free radicals are destructive molecules, which might seem like a bad thing until you consider that those free radicals induce a hormetic response where your antioxidant system is ramped up to counter them. As a result, every time you exercise, your mitochondria are drenched in the potent antioxidant elixirs that only our body can make.

Protein Intake

With protein intake we want a high protein diet to increase m-TOR activation. But there again is a sweet spot. We don’t want to be constantly activating this pathway if we do it has been linked to increased mortality rates. Particualry if you are having constant high protein intake with one amino acid- Leucine. As Leucine is a potent activator of M-TOR. And if constantly stimulated it can increase the ageing process. Now don’t freak out if we didn’t activate M-TOR we will become frail. If you don’t have muscle going into your older age it will increase mortality. We need enough muscle but not too much. One of the big markers for morality is muscle mass. So think about the frail old lady- if she gets an infection it’s going to be much harder for her to fend this off compared to someone who is fit and healthy and larger at the same age.

Protein is made up of amino acids and Methonine is another amino acid that seems to be linked with ageing (not just Leucine). High intake of Methionine has been linked to increased ageing. Meat and animal products have higher levels of methionine than plant proteins. We want to as said earlier activate M-TOR but not too much. Which maybe why Pea proteins could be a good alternative to whey based products. Having said that meats are a more complete source of protein than plant based sources and more easily uptake and digested. Its not one way is better than another if you are vegetarian for example for various reasons. But how can we work with that to optimise your protein intake given we know protein is anti-aging.

Salmon- Contains a compound called Astroxanthan - which is a potent activator of NRF2. But it isn’t as good at activating NRF2 as surfurophane. We don’t know yet if we gt additional benefits by activating this pathway through multiple ways or whether one is enough.

Creatine

Is one of the few supplements that has evidence in the sports world. The international society of sports nutrition concluded it is the most effective supplement available to date to increase lean body mass & increasing high intensity exercise capacity. It also reduces muscle damage and enhances recovery from intense exercise. Whilst it did have it’s issues it has been shown to increase memory in older adults ( there is a great paper on Alzheimers about this).

In terms of safety studies up to 5 years have shown no adverse effects in taking this. The myth is it increases hair loss but this has been proven invalid.

So how much creatine? I feel it needs its own post to go into more detail but 5g daily is beneficial for most adults.

Collagen Supplements

There is now a meta-analysis for 10 different randomised trials that show improved overall skin health including: moisture, elasticity and reduced wrinkle number. 10-15g appears to be the recommended amount to reach these benefits.

Hyaluronic acid for skin

Is the backbone of our connective tissues. It helps build up cartilage, assists with blood vessel health & also has shown promise in anti-aging. The amount in our skin decreases as we age. A 75 year olds skin is found to have on average 1/4 the amount that a 19 year old has. We have multiple randomised controlled trials that show in humans that hyaluronic acid improves skin health. The latest to come out in 2021 compared to placebo to hyaluronic acid supplements and hyaluronic acid improved water content of the skin, reduced wrinkles and skin elasticity. There was a fear it would increase cancer growth by supplementing! Not what we want right! But a trial in mice that had tumours helped show there was no proof of such theorised effects. 200mg daily is what is currently recommended for these effects.

Keto diet

At the moment the evidence is lacking to stay in a ketotic state, but it appears the keto diet just helps people achieve their protein targets and not over consume carbohydrates- this in turn keeps their blood glucose levels more stable. I’ll talk about myths with diets but no diet is superior to any other- it really does come down to some basic principles such as: eat adequate meat/protein (not excessive), enjoy some fats (preferably from plants sources), eat carbohydrates not to excess ( as this is often where people go to excess causing erratic blood glucose levels, weight gain due to excessive calorie intake of carbs). Carbs are protein sparing so we don’t want to cut them out of our diets and we also need them for energy. Again no food group or food is inherently bad it’s just do those nutrient components in that food meet my needs? That should be the question we ask rather than being so judgmental about food.

Fibre

Psyllium husk 5-10g is one supplement outside of gaining fibre through the diet that can help feed our micorbiome. See my previous post on why the gut microbiome is so important. A 2016 Cochrane review showed it lowered total cholesterol and LDL cholesterol when you have increasing fibre intake. It also helps keep you feeling fuller for longer.

At the moment we don’t know if there is certain strains of gut bacteria we should be enhancing to improve longevity. But increasing fibre in the diet in general, not artificial sweeteners but soluble and insoluble fibre appears to have the most benefits. The trouble with artificial sweeteners is when the gut bacteria expend energy eating these articifical sugars there are no calories that come from them using energy to eat them,. As the gut bacteria didn’t receive any energy it causes a cascade of signalling to make you feel even more hungry and unfortunately studies have shown people that eat artificial sweetens like Sucralose often end up eating more calories than those who just ate the sugary products due to this. Does that mean they are bad? No. It just means you might need more self control or hey just eat the sugary item but in a smaller portion to satiate that craving. Because trying to trick you gut bacteria just makes them more noisy and demanding. So pick your battle here.

Berberine and Metformin

Both stimulate AMP-K. Metformin is a diabetic medication-so we have seen this in the fact that metformin can increase weight loss but on the flip side metformin decreases the exercise benefits. Exercise increases M-TOR and Metformin stimulates AMP'-K so it was canceling out the benefits. At the moment there is more evidence around metformin due to the extent of patients with type 2 diabetes compared to berberine (which is a herbal product). If you are going to use these to stimulate AMP-K you would want to use these product on your rest days not training days. They are currently undertaking a trial using metformin in healthy patients to see what effect it has on longevity.

Insulin/anti-diabetics

High levels of insulin accelerates ageing. Now if you have high sugar in the diet and have diabetes for example having that sugar run rampant in your body causes a lot of inflammation and damage to cells. So it’s not as simple as if you are a diabetic stop insulin to slow ageing. Type 1 diabetics can’t make insulin and they would die if they stopped using it. Type 2 that end up on insulin its because they have lost sensitivity to insulin and caused damage to the pancreas from lifestyle choices not a genetic condition per say. Caveat to this is people can have predisposition to developing type 2 diabetes but that just means they need to be even more conscious of the lifestyle and diet choices to avoid that developing. Because the damage excess sugar does to cells is far more detrimental than extending life . But high insulin levels are not great for the ageing process and so we want to have a diet for example that doesn’t cause constant spikes or keep big swings in variation.

SGLT2 Inhibitors eg empagliflozin show promise for anti-aging by avoiding this scenario. As they essentially help make the kidneys excrete glucose . They are having positive results on heart disease and kidney disease. But the verdict is out on whether they will help with ageing affects. GLP-1 receptor agonists eg. exenitide helps patients to feel fuller for longer and is also used in diabetes management. It is showing promise for patients keeping weight off over the long term (yrs).

I’ll say it again diabetes is a topic on its own. It’s important for type 1 to have insulin as they can’t make it on their own and they can die if they don’t have their medication and when it comes to type 2 we need to be advocating diet and lifestyle changes such as exercise to reverse this metabolic disease. If we can control lifestyle factors we can stop the need for insulin use in type 2.

Resveratrol

In 2003 it gained a lot of traction, this particular polyphenol and its research and was going to assist with heart disease and longevity. But the trial data so far is lacking, the data in mice looked promising but that hasn’t translated into the long term data in humans so far.

While we are talking mice studies- Dr David Sinclair injected transcription factors into the eyes of mice that were ageing and reversed the eye ageing damage. These factors are working on the autophogy pathway.

Omega 3

The Mayo clinic recently published a meta-analysis that showed it statistically significantly reduced in the risk of heart attacks with high grade certainty. So fish oil is great for your cardiovascular function- so enjoy your oily fish.

TMG (Trimethylglycine)

A meta- analysis looking at risk factors for dementia -one of the main risk factors was high level of homocysteine in the blood. By taking TMG we can lower homocysteine. TMG is found in foods such as beets, spinach and whole grain breads. 100-300mg daily should be the target for TMG to have this dementia lowering effect.

Glycine and NAC

From the age of 45years the effect of anti-oxidants from our body appear to decrease and the levels of glutathione decrease. Glycine and NAC are building blocks for glutathione, that older adults when supplemented with these two supplements corrected their glutathione levels and improved their mitochondria performance or power health of their cells. Does this mean you need NAC? Not unless you are over 45year or know your levels are low.

There are many other multivitamins in smaller amounts but another day that’s enough for now right :P

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anti-ageing, healthCourtney DixonFebruary 13, 2023anti-ageing, nad, m-tor, protein, keto, nutrition, drug, suplements

Anti- Ageing Supplements, Drugs and Nutrition - are they real & do they work?

How are we trying to stop ageing and is it possible?

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