MultiV – our “basic” MVM (Multiple Vitamin-Mineral with additional nutrients) has been updated, rebalanced and made over to be even more powerful than before, with significant changes based on the latest nutrition science and experiential feedback. MultiV is comprehensive – 26 essential vitamins & minerals and four important extracts of 32 foodstuffs. With all those nutrients flying around, which ones are the most important? The sexiest? The major drivers for exercise performance and recovery? Here, we break them down and hit you with the highlights.

Let’s get sexy.

MultiV Major Drivers: The Iron Enigma

Iron is super-essential for generating energy from oxygen and all those carbs you eat, making it critical for endurance athletes. Iron is also widely regarded as the #1 problem with micronutrients and exercise.

Among women and men who exercise, iron still shows a 15-50% and 5-30% deficiency rate, respectively. You would think that dietary advice, simply taking a multiple vitamin-mineral (MVM) with iron, or popping an extra stand-alone iron supplement would fix that issue, but no! The iron problem persists. An Iron Enigma. 

Recent research has characterized the prevalence of LEA (Low Energy Availability) in women and RED-S (Relative Energy Deficiency in Sport) when you train very hard and/or do not consume enough energy/calories (carbs). LEA/RED-S is associated with low iron stores, low hemoglobin (red blood cells), and even anemia (low blood cells) – even with “adequate” iron intakes. Massive iron supplementation/therapy can restore iron and performance levels, but inflammation from excess iron due to these options is an unresolved, haunting issue – the root of the Iron Enigma.

This is all because iron is like a biological, double-edged sword. Laws of Nature mandate that iron atoms are always stuck on a protein and not solubilized, or else, problems ensue. But even tiny amounts of iron loosened from its enzymes, storage and transport proteins can start chain reactions that make thousands of hydroxyl radicals and thousands of damaged cellular proteins and structural components. Compensatory inflammation sends an alert: Damage! Send Help! Part of the help message triggers the rapid release of a protein called hepcidin, a master regulator of iron metabolism that ironically impedes your body’s ability to get the iron that it needs when it needs it most.

The solution to the Iron Enigma is two-fold:

  1. provide hydration/carb/electrolyte supply during exercise to reduce or delay iron-caused inflammation; and
  2. ensure a consistent, steady, non-exorbitant intake of iron from a true chelate – Ferrochel®.

Obviously EFS and EFS-PRO address the former, and the new MultiV addresses the latter better than any formula we – or anyone else – has produced before.

Hip with Hep

One of the quietest BIG STORIES in human nutrition has been the realization that iron metabolism is actually psychotically controlled by a recently identified protein “hormone” named hepcidin. Though it’s still too “new” for textbook understanding, hepcidin has a small but growing number of studies and comprehension. In particular, it has been a revelation for tying together the Iron Enigma with energy metabolism problems, including carb/fat controversies.

When released, hepcidin works fast to choke off the biggest channels of iron supply, transport, and movement. It does so by removing ferroportin (iron transport protein) from membranes of key tissues, DECREASING the amount of iron absorbed by your gut, that gets recycled by immune system macrophages (garbage collectors and recyclers) and that is sent into circulation from gut, liver and red blood cells.

Hepcidin’s role is to prevent oxidative toxicity from spreading further via loose iron; however, since intense exercise, overexertion and running out of carbs for muscular energy production normally cause iron-induced inflammation resulting in cell and tissue nano/microdamage, hepcidin explains why iron is still a specific problem for endurance exercisers. The harder you work, the less your body can utilize iron, but the more your body needs it – again, the Iron Enigma.

Hepcidin even explains why the usual iron treatments with soluble iron salts like ferrous sulfate need exorbitant doses and have side effects – those salts easily let iron loose, flooding your system and triggering hepcidin release. That only compounds the very reason for taking iron, and it necessitates large doses of iron from soluble salts to overwhelm the hepcidin, which is only released in response to those large doses, for any hope of a desired effect.

Trying to overwhelm hepcidin with iron from soluble salts artificially inflates iron storage protein levels (ferritin and others) without giving your muscles the iron they need (myoglobin), effectively tricking blood tests into showing that you are replete with iron. But! Your muscle mitochondria, which is where you really want the iron, are showing otherwise. Your muscles don’t use ferritin. Instead, they use intracellular myoglobin as a storage protein to feed mitochondria iron during both performance and recovery.

Here’s the takeaway: Even if you overwhelm hepcidin with soluble salts, the only benefit you’ll see is in blood tests, not endurance performance – one last wrinkle for the Iron Enigma.

The Right Iron

Ferrochel® is the right iron for solving the Iron Enigma. As a true chelate of ferrous iron with two glycine amino acids, Ferrochel® has been shown to mete out iron absorption depending on your body needs – more if you need iron, less if you are replete or overloaded.

Ferrochel® has improved the major marker for ultraendurance performance – more red blood cells (read: hematocrit, hemoglobin, RBC counts) and fewer markers of free radical damage. Human studies have found that Ferrochel® iron is also more potent than other iron forms, meaning lower doses are more effective and reducing the risk of iron overload triggering hepcidin release that squelches iron delivery to your body’s iron performance centers: bone marrow and muscles. 

Hepcidin explains why very high amounts of ferrous salts like sulfate and others are needed to restore iron markers and status in order to overcome the Iron Enigma; the chelated iron in Ferrochel® avoids this risk by only letting your body take the iron it needs rather than flooding your system with an unnecessary – and counterproductive or potentially toxic – iron overload.

Ironic Sidenotes

As mentioned above, fuel supply also affects iron metabolism. Newer evidence in ultraendurance athletes has found that low carb diets (keto diets) make more hepcidin activity, which ultimately impedes iron efficacy via the Iron Enigma. High carb diets and high carb usage during endurance exercise lowers hepcidin, which helps athletes get the increased iron supply they need for peak performance. This helps to explain findings of hundreds of human studies on benefits from carb supplementation during exercise and recovery – and why keto manipulation during exercise is falling out of favor. For effective iron metabolism, take your EFS and Liquid Shots!

Similarly, polyphenol antioxidants limit hepcidin release after exercise, likely by reducing inflammation caused by free radicals and tying up loose iron. This argues strongly for benefits from Spectra® (loaded with hundreds of polyphenol types from concentrates/extracts of 29 fruits/vegetables/spices/herbs), Ginkgo polyphenols, and Green Tea catechins (another type of polyphenol) in the updated MultiV – yet another way MultiV helps reduce effects of loose iron and maintains performance and recovery.

Citations: Alfaro-Magallanes ; Badenhorst 2015 2215, 2015 2521, 2022; Dominguez 2018; Drakesmith 2012; Ganz 2012; Grijota 2022; McKay 2019 548, 2019 635, , 2020; Nemeth 2006; Peeling 2009, 2014, 2017; Sim 2014, 2019

MultiV Major Drivers: The Right Folate

Funky folate is a series of closely related molecules that rearrange themselves in an infinite metabolic cycle, called the folate cycle, which involves variations on a single carbon molecular unit. That single carbon unit is vital for life, needed for making DNA and RNA, marking genes for expression or shutdown, and for making dozens of compounds you need for health and life itself.

In MultiV, we changed from folic acid to the real, biologically correct folate – 5-Methyltetrahydrofolate (MTHF) – for many good reasons. In nature, folic acid is an inactive intermediate formed briefly in the synthesis pathway to active folates (MTHF); but folic acid added to foods and dietary supplements is always just that, added, and it’s synthesized, not naturally produced. Your foods contain no folic acid unless it’s added artificially. Your cells and bloodstream normally contain no folic acid.

So why did the Daily Value (it’s now Dietary Folate Equivalents or DFEs) specify folic acid? Because folic acid mostly works like actual folate, is cheaper to make commercially, and has been incorrectly supposed to be more stable than other folates. Yes, mandatory folic acid fortification of flour has reduced the incidence of serious birth defects and macrocytic anemia – but not completely, as hoped.

MultiV skips the folate middleman

Your body and all other living creatures need to go through several steps to activate folic acid into MTHF. MultiV is formulated to skip this process, because the process is suboptimal or deficient in 30% or more of the population with common genetic variations.

With high folic acid intakes (but not MTHF intakes), unmetabolized folic acid (UMF) can build up and interfere with active folate forms. This interference decreases overall folate function when intakes and levels look normal or high, effectively causing a folate deficiency. Using MTHF doesn’t reduce this risk; it altogether eliminates it.

In addition to bypassing any issues caused by those genetic variations, MTHF is also about 1.7 times stronger than folic acid, and the particular calcium MTHF form used in MultiV is a stable form. It’s simply an all-around superior folate. It’s already active without requiring an additional (and very fallible) internal process, it’s readily bioavailable, and it’s ready to work in the folate cycle.

Citations: (Bailey 2007; EFSA 2009, 2010; Fenech 2005; Ganz 2017; Health Canada 2009; Hoch 2009, 2010; Imbard 2013; Knowles 2016; Lintas 2019; Marchetta 2015; ODS 2022; Prinz-Langenohl 2009; Scaglione 2014; Selhub 1996; Stahl 2008; Stanhewicz 2017; Thuesen 2010; Tsang 2015; Ulrich 2006; USFDA 2017; Woolf 2006)

MultiV Major Drivers: Spectra® Antioxidant Blend

Antioxidants are both revered and reviled in exercise research and practice.

At first, antioxidants were hailed as the answer to the free radical-induced damage that normally results from overexertion. But years of study swung the pendulum back to where antioxidants can backfire and impede training adaptation. Today, we know that your body needs an initial free radical storm to initiate repair, healing, and adaptive processes, and squelching oxidation would effectively limit that operation. The trick is balance, not extreme polarity.

At First Endurance, we realized that the research on antioxidants and exercise has mostly missed the boat of reason because of the tendency to swing back and forth and a limited approach to methodology. Specifically, giving ever-increasing amounts of one or maybe two or (very seldomly) three antioxidants makes for easier study using reductionist methodology, but it doesn’t demonstrate how our bodies actually utilize antioxidants. All they prove is that too much of any specific antioxidant impedes repair, healing, and adaptive processes too much. The reason? Overloading a single antioxidant source imbalances the integrity of the whole network of interactive and intersupportive antioxidant pathways.

This has given us fear-mongering, out-of-context and nonsensical understandings about antioxidants causing all sorts of bad things to happen, ending with do not take antioxidants if you exercise. Talk about throwing the baby out with the bath water – sheesh!

We pulled together an overview of what our body sees and does when intensely exercising during long durations. And piecing together the fractious, contradictive, scattered, and sometimes cherry-picking research shows that multiple, food-based antioxidants can prevent muscular soreness and improve biomarkers of recovery, showing that the right dose of the right antioxidants can improve normal exercise-induced training adaptations and reduce muscular damage from overexercise. To build the MultiV formula, we built a guiding list of “more”:

  • More antioxidants (to the extent of healthy diet levels)
  • More kinds of antioxidants (as many types as possible)
  • More MOAs (Mechanisms Of Action)
  • More supportive interactions, bioavailability, compartmentalization, and dose-response

The components in this list of more all conspire to lead to more balance across the repair, healing, and adaptive processes.

Diversity rules!

To start, we went back to nature for inspiration, dramatically increasing the number of food-based antioxidants in the polyphenol complex from eight to much more than 29 with the Spectra® Total ORAC5 Antioxidant Blend – almost quadrupling down on the “more kinds of antioxidants” item from our list of more.

We also kept the potent flavonoid and biflavonoid classes from green tea and Ginkgo, and we decreased the total amount needed by using more concentrated sources – a move that ensures MultiV’s antioxidant load doesn’t impede adaptative processes.

Spectra® is also supported by a host of other antioxidant ingredients. We boosted vitamins C and E enough for desired actions, but only to amounts shown by studies on human physiology to not interfere with training adaptation or recovery. We also changed the selenium source to L-Selenomethionine, which is (deep breath) the key cofactor of what is quantitatively the most important cellular antioxidant enzyme: GPX (Glutathione Peroxidase). Finally, we made sure that MultiV fit well with other First Endurance antioxidant products, such as HALO, Pre-Race, and the Optygens – full synergy across the entire FE system.

Of the above, it’s worth dwelling on the Spectra® Total ORAC5 Blend – after all, it’s the headliner of this section. We found that Spectra® was the answer to provide a range of food antioxidants in a small amount, which in turn provides balanced overall (total) antioxidant activity.

In human clinical studies on healthy, sedentary men and women, a 100mg dose of Spectra® lowered free radical concentration in blood serum and blood cells significantly at one, two, and three hours compared to the placebo group. All but one (11/12) Spectra® subjects showed decreases, but only 5/12 placebo groups showed decreases, and these decreases were lesser than those of the Spectra® group.

A second randomized, crossover, placebo-controlled human clinical study with 22 healthy subjects showed decreases of the four major types of free radicals (technically called ROS, Reactive Oxidative Species). Again, taking Spectra® showed decreases in the ROS at one, two, and three hours. In another type of test, blood cells were collected and stimulated with TNF-alpha, an inflammatory cytokine known to raise ROS levels in cells. Spectra® reduced the ROS generated by blood cells after TNF-alpha stimulation, which can be interpreted as an antiinflammatory response.

In summary, Spectra® has shown potent, balanced, broad-spectrum, fast-acting (one hour) antioxidant activity in humans against the major ROS normally present at rest and after inflammatory stimulation.

Citations: (Bentley 2015; Carey 2021; Devrin-Lampir 2020; Lamprecht 2009; Li 2022; Mrakic-Sposta 2020; Nemzer 2014 647, 2014 828; Petrov 2022; Rickards 2021; Schneider 2018; Toro-Roman 2022)

MultiV Major Drivers: Choline, New Kid on the Block

Finally, choline has become an officially anointed Essential Nutrient, with its own Daily Value (550mg). Although your body makes some choline, it does not make enough to maintain all the functions it’s involved in. Perhaps the luster of choline went unrecognized because of all the important roles it plays, making shorthand impact essentiality difficult to show – it’s that critical.

Your body does not agree with stuffed-shirt regulators who denied choline essential status because of ignoring the basic physiological facts about dietary need. Choline as such (not choline in phosphatidylcholine as found in krill oil and lecithin) mostly ends up as the neurotransmitter acetylcholine, which triggers muscular contractions and nervous impulses. Choline works closely with folate and B12 to bolster the folate cycle and all its important products (see Folate above). The impact on endurance performance is clear.

Blood choline levels are reproducibly decreased during long-duration endurance running (more than 2-3 hours). When administered, choline supplementation sometimes increased exercise performance. Whether that was an effect of increasing choline in the system or repleting choline to correct a deficiency, well, the effect is the same.

Regarding general health, a deficiency of choline intake is also linked to humans developing fatty liver, which is interesting since in the USA there is an epidemic of fatty livers – and high folic acid intakes – via junk food fortification. Also, like folate, there are a number of common genetic variations of enzymes that utilize choline, and others linked to estrogen levels (a problem after menopause), decreasing its overall functions. 

MultiV has an amount of choline (as the ester of natural form tartrate) – 10% of DV – to push intakes of a plurality of persons above the EAR (Estimated Average Requirement), suggesting it will produce those positive performance benefits.

Citations: (Atzler 1935; Bucci 1993; Buchman 1999, 2000; Conlay 1986, 1992; de la Huerga 1951, 1952; Deuster 2002; Ganz 2017; Garrow 2007; Hirsch 1978; Hoeg 2020; Jager 2007; Martinez 2016; Mies 1958; Moretti 2020; Naber 2015; Newsom 2016; ODS 2022; Penry 2008; Sandage 1992; Spector 1995; von Allworden 1993, 1995; Wallace 2018; Warber 2000)


These four standout nutrients – mineral, vitamin, quasi-vitamin, and food concentrates – provide additional benefits by using the right forms. The additions and changes of just these four nutrients assure prime health that also positively impacts exercise performance and recovery.


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December 22, 2022 — Luke Bucci
Tags: research

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